Integrated container for lyophilization, rehydration and processing of biological materials

Abstract

An apparatus to lyophilize, store, transport, rehydrate, and process aqueous biological materials in a container which maintains sterility of its contents, allows container shrinkage after lyophilization, and optimally permits filtration or dialysis of the contents in situ, without the need for a second or series of additional containers. These benefits are met by a microporous container constructed of a membrane that is water vapor permeable, yet water impermeable.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The invention relates to the use of an integrated container for lyophilization, storage, distribution, and processing of fluids, cells or tissues.[0003]2. Description of Related Art[0004]Distribution of materials requires storage under conditions suitable for optimum product stabilization, minimum storage cost, and simple operation at site of use. This is of particular importance in the field of biopharmaceuticals because of the propensity of such products to lose their biological activity in the liquid, aqueous state. Cooling below −20 degrees Celsius (° C.) is a popular approach, but costs of maintaining the materials at reduced temperatures (−20°, −80° or −196° (C.)) for extended periods and during transport are high. Additionally, many important biological products, such as blood and plasma, have high mass (weight), which in turn creates the shipping challenges of logistics and expense.[0005]A typical example of a b...

AI Technical Summary

Benefits of technology

[0013]The present invention is an apparatus to lyophilize, store, transport, rehydrate, and process aqueous biological materials in a container which maintains sterility of its contents, allows container shrinkage after lyophilization, and optimally permits filtration or dialysis of the contents in situ, without the need for a second or series of additional containers. These benefits are met by a microporous container constructed of a membrane that is water vapor permeable, yet water impermeable.

Problems solved by technology

Cooling below −20 degrees Celsius (° C.) is a popular approach, but costs of maintaining the materials at reduced temperatures (−20°, −80° or −196° (C.)) for extended periods and during transport are high.

Additionally, many important biological products, such as blood and plasma, have high mass (weight), which in turn creates the shipping challenges of logistics and expense.

Transporting blood plasma per se is problematic due to the need for temperature controls and due to the high mass of its primary constituent, water.

Even when blood plasma is lyophilized to remove the water and its attendant disadvantages, storage, transport and processing for use become no easier because the container is fixed prior to lyophilization and because of the documentation and rehydration requirements of such products.

The water vapor is removed via a connection to the neck of the container, with storage and shipment resulting in large amounts of wasted space, namely, the space formerly occupied by the water.

Aseptic conditions are essential, but many manipulative steps can compromise sterility.

The disadvantages of this approach include the large size of the container to be stored, the fragility of the glass container, and the difficulty of maintaining aseptic conditions during the process.

First, containers are not provided in a sterile condition but contain specific instructions that any such sterilization is the sole responsibility of the user.

Steam sterilization can be used, if necessary, but other useful procedures are either not recommended (e.g., radiation techniques) or are not addressed (e.g., ethylene oxide, gas plasma, formaldehyde gas, hydrogen peroxide vapor).

Second, after removal of the water, the container is returned to the atmosphere, and the product cannot be stored under a vacuum due to the “open” nature of the ePTEE materials.

Fourth, the rigid nature of the tray system precludes the integration and use of such a system into processes that involve centrifugation and decantation of fluids and cell suspensions (e.g., blood cell fractionation).

Finally, the approach does not allow for facile exchange of the solution after lyophilization (e.g., removal of mannitol).

This precludes the use of a single package for the storage and delivery of cells by infusion.

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